Technical Field
The present invention relates various embodiments of a composition, method, system, and kit for optical electrophysiology. More specifically, the present invention relates to enhanced mapping (and/or optical imaging) of thick tissue with novel near infrared probes (voltage-sensitive dyes) having high voltage sensitivity, including said composition, method, system, and kit for advanced optical methods detailing the electrical activity of an organelle, a cell, a plurality of cells, a tissue, or an organ, including cardiac tissue and neurological tissue.
Related Art
A common method for optically imaging the heart tissue of a subject's body is by using microelectrode or patch clamping techniques with branch electrodes. To utilize branch electrodes, multiple leads are used to insert needles into various portions of the heart muscle wall. Once the needles are in place, they record from isolated points inside the muscle. However, branch leads have limitations and drawbacks to their use. Branch leads damage portions of the heart muscle, penetrate the tissue (thereby disrupting cross-sectional continuity), and provide uneven measurements due to the size and displacement of the needles from one another.
These disadvantages have led, in part, to the development of styryl dye, di-4-ANEPPS, which is a voltage-sensitive dye. This dye has been used for optically imaging tissue, including cardiac tissue. However, the di-4-ANEPPS dye has limitations in its use as a voltage probe for cardiac electrophysiology in cells and tissues. Di-4-ANEPPS cannot penetrate thick tissue at depth; di-4-ANEPPS will only afford measurements of optical potentials from only a few hundred micrometers of subsurface layer of tissue. Also, as the excitation wavelength of di-4-ANEPPS is the same range in which blood and tissue typically absorb, at 450 to 550 nanometer range in the electromagnetic spectrum, measurements taken with di-4-ANEPPS typically have high scattering and noise with a low optical resolution, resulting in low image quality even with very high light intensity. Hence, a need exists for voltage-sensitive probes that excite and emit electromagnetic radiation in an electromagnetic range removed from biological interference (i.e. decreased scattering and noise) and provide in depth imaging of thick tissue and/or blood-perfused tissue.